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ExAblate Blood-Brain Barrier Opening for Treatment of Alzheimer's Disease

Primary Purpose

Alzheimer Disease

Status

Recruiting

Phase

Not Applicable

Locations

Canada

Study Type

Interventional

Intervention

Blood Brain Barrier (BBB) Disruption

About this trial

This is an interventional treatment trial for Alzheimer Disease focused on measuring Magnetic Resonance guided Focal Ultrasound (MRgFUS), Alzheimer's Disease, ExAblate, Blood Brain Barrier

Eligibility Criteria

50 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Male or Female between 50-85 years of age
Probable Alzheimer's Disease (AD)
If taking concurrent Alzheimer's medication, has been on the medication for at least 2 months with a stable dose for at least 3 months
Able to communicate sensations during the ExAblate MRgFUS procedure
Ambulatory

Exclusion Criteria:

MRI Findings
Presence of unknown or MR unsafe devices anywhere in the body
Significant cardiac disease or unstable hemodynamic status
Relative contraindications to ultrasound contrast agent or PET amyloid tracer
History of a bleeding disorder
History of liver disease
Known cerebral or systemic vasculopathy
Significant depression and at potential risk of suicide
Any contraindications to MRI scanning
Any contraindication to lumbar puncture for collection of cerebral spinal fluid
Untreated, uncontrolled sleep apnea
History of seizure disorder or epilepsy
Severely Impaired renal function
Currently in a clinical trial involving an investigational product or non-approved use of a drug or device or in any other type of medical research
Chronic pulmonary disorders
Positive human immunodeficiency virus (HIV)
Known apolipoprotein E allele (ApoE4) homozygosity

Sites / Locations

Division of Neurosurgery, Sunnybrook Health Sciences CentreRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Blood Brain Barrier (BBB) Disruption

Arm Description

The ExAblate Model 4000 Type 2.0 System

Outcomes

Primary Outcome Measures

Device and procedure related adverse events

Rate of adverse events following each treatment through end of study

Secondary Outcome Measures

BBB Disruption and Closure

MRI images post ExAblate treatment to verify that the BBB was disrupted and subsequently closed

Change in Alzheimer's Disease Assessment Scale-Cognition

Mental cognition assessment

Change in Amyloid Tracer uptake

PET scan analysis comparing the Amyloid Tracer uptake on images taken at baseline and after the last treatment

Full Information

NCT ID

NCT03739905

First Posted

November 2, 2018

Last Updated

February 28, 2023

Sponsor

InSightec

Collaborators

Focused Ultrasound Foundation

1. Study Identification

Unique Protocol Identification Number

NCT03739905

Brief Title

ExAblate Blood-Brain Barrier Opening for Treatment of Alzheimer's Disease

Official Title

A Phase IIa Study to Evaluate the Safety and Efficacy of Blood-Brain Barrier (BBB) Opening Using Transcranial MR-Guided Focused Ultrasound in Patients With Alzheimer's Disease

Study Type

Interventional

2. Study Status

Record Verification Date

February 2023

Overall Recruitment Status

Recruiting

Study Start Date

December 6, 2018 (Actual)

Primary Completion Date

December 2024 (Anticipated)

Study Completion Date

December 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

InSightec

Collaborators

Focused Ultrasound Foundation

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of the ExAblate® Model 4000 Type 2.0 system as a tool to open the blood-brain barrier (BBB) in patients with probable Alzheimer's Disease (AD).

Detailed Description

This study is a prospective, open label, single-arm, non-randomized, phase IIa trial to evaluate the feasibility, safety and efficacy of repeated, BBB opening using the ExAblate® Model Type 2.0 (220 kHz) system. Patients with diagnosis of Probable Alzheimer's Disease may qualify for a clinical trial to have three serial ExAblate BBB disruption procedures in specific areas in the brain.This study will be conducted at a single center in Canada and will enroll up to 30 patients.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Alzheimer Disease

Keywords

Magnetic Resonance guided Focal Ultrasound (MRgFUS), Alzheimer's Disease, ExAblate, Blood Brain Barrier

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Blood Brain Barrier (BBB) Disruption

Arm Type

Experimental

Arm Description

The ExAblate Model 4000 Type 2.0 System

Intervention Type

Device

Intervention Name(s)

Blood Brain Barrier (BBB) Disruption

Other Intervention Name(s)

ExAblate Neuro

Intervention Description

Focal Ultrasound (FUS) involves the application of acoustic energy at low frequencies from over 1000 individual transducers into distinct targets to induce BBB disruption.

Primary Outcome Measure Information:

Title

Device and procedure related adverse events

Description

Rate of adverse events following each treatment through end of study

Time Frame

6 months

Secondary Outcome Measure Information:

Title

BBB Disruption and Closure

Description

MRI images post ExAblate treatment to verify that the BBB was disrupted and subsequently closed

Time Frame

Immediately after the end of each ExAblate treatment and 24 hours after each treatment

Title

Change in Alzheimer's Disease Assessment Scale-Cognition

Description

Mental cognition assessment

Time Frame

Baseline and 6 months

Title

Change in Amyloid Tracer uptake

Description

PET scan analysis comparing the Amyloid Tracer uptake on images taken at baseline and after the last treatment

Time Frame

Baseline and Day 8 following the third treatment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

50 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Male or Female between 50-85 years of age Probable Alzheimer's Disease (AD) If taking concurrent Alzheimer's medication, has been on the medication for at least 2 months with a stable dose for at least 3 months Able to communicate sensations during the ExAblate MRgFUS procedure Ambulatory Exclusion Criteria: MRI Findings Presence of unknown or MR unsafe devices anywhere in the body Significant cardiac disease or unstable hemodynamic status Relative contraindications to ultrasound contrast agent or PET amyloid tracer History of a bleeding disorder History of liver disease Known cerebral or systemic vasculopathy Significant depression and at potential risk of suicide Any contraindications to MRI scanning Any contraindication to lumbar puncture for collection of cerebral spinal fluid Untreated, uncontrolled sleep apnea History of seizure disorder or epilepsy Severely Impaired renal function Currently in a clinical trial involving an investigational product or non-approved use of a drug or device or in any other type of medical research Chronic pulmonary disorders Positive human immunodeficiency virus (HIV) Known apolipoprotein E allele (ApoE4) homozygosity

Facility Information:

Facility Name

Division of Neurosurgery, Sunnybrook Health Sciences Centre

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M4N 3M5

Country

Canada

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Allison Bethune

Phone

416-480-6100

Ext

4831

allison.bethune@sunnybrook.ca

First Name & Middle Initial & Last Name & Degree

Nir Lipsman, MD, PhD

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

34815790

Citation

Mathew AS, Gorick CM, Price RJ. Multiple regression analysis of a comprehensive transcriptomic data assembly elucidates mechanically- and biochemically-driven responses to focused ultrasound blood-brain barrier disruption. Theranostics. 2021 Oct 11;11(20):9847-9858. doi: 10.7150/thno.65064. eCollection 2021.

Results Reference

derived

PubMed Identifier

33693781

Citation

Meng Y, Pople CB, Suppiah S, Llinas M, Huang Y, Sahgal A, Perry J, Keith J, Davidson B, Hamani C, Amemiya Y, Seth A, Leong H, Heyn CC, Aubert I, Hynynen K, Lipsman N. MR-guided focused ultrasound liquid biopsy enriches circulating biomarkers in patients with brain tumors. Neuro Oncol. 2021 Oct 1;23(10):1789-1797. doi: 10.1093/neuonc/noab057.

Results Reference

derived

Learn more about this trial

ExAblate Blood-Brain Barrier Opening for Treatment of Alzheimer's Disease

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